A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium

Nature Communications
Ksenija SlavicMaria M Mota

Abstract

Iron is an essential micronutrient but is also highly toxic. In yeast and plant cells, a key detoxifying mechanism involves iron sequestration into intracellular storage compartments, mediated by members of the vacuolar iron-transporter (VIT) family of proteins. Here we study the VIT homologue from the malaria parasites Plasmodium falciparum (PfVIT) and Plasmodium berghei (PbVIT). PfVIT-mediated iron transport in a yeast heterologous expression system is saturable (Km ∼ 14.7 μM), and selective for Fe(2+) over other divalent cations. PbVIT-deficient P. berghei lines (Pbvit(-)) show a reduction in parasite load in both liver and blood stages of infection in mice. Moreover, Pbvit(-) parasites have higher levels of labile iron in blood stages and are more sensitive to increased iron levels in liver stages, when compared with wild-type parasites. Our data are consistent with Plasmodium VITs playing a major role in iron detoxification and, thus, normal development of malaria parasites in their mammalian host.

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Citations

Sep 30, 2016·Frontiers in Plant Science·Wei ZhuShengyi Liu
Jun 16, 2018·PLoS Pathogens·Maria Fernanda Laranjeira-SilvaNorma W Andrews
Feb 12, 2019·Nature Plants·Takafumi KatoOsamu Nureki
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Jun 8, 2021·Microbiological Research·Behnoush KhasheiiAbdolmajid Mohammadzadeh

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Methods Mentioned

BETA
transfection
flow cytometry
PCR
transgenic
genotyping

Software Mentioned

ClustalW2

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